Phenylpropanolamine (PPA) is a sympathomimetic drug and the major ingredient in nonprescription diet medications. The cardiovascular and psychological effects of this drug for women have not been adequately studied, even though women are the primary consumers of PPA diet aids. For both women and men, little is known about the effect of PPA with caffeine or under conditions of stress. The major health-related goal of this proposal is to provide new information on the safety of PPA by determining effect in women, and in subgroups of men and women who may be at risk for adverse reactions i.e. oral contraceptive (OC) users and individuals with a family history of hypertension (FH). The proposed research will also investigate responses to PPA during stress, the therapeutic index of PPA by evaluating responses to a double dose, and whether PPA increases sympathetic nervous system (SNS) activation. The questions to be addressed arise from data indicating significant effects of PPA on the cardiovascular system and will further define these effects in relation to risk factors for hypertension. Experimental studies using double-blind, randomized, placebo-control designs will investigate PPA effects. Study 1 will examine effects of 150 mg PPA sustained release (sr), 75 mg PPA sr, and 75 mg PPA sr + 250 mg caffeine, or cardiovascular and psychological reactions under resting conditions, in 24 women users and 48 age-matched normally cycling (NC) women (24 tested during the follicular phase and 24 tested during the luteal phase), with half of each group caffeine users and nonusers, to determine if reactions to PPA or PPA plus caffeine produce: increases in blood pressure; increases in SNS activation; increases in positive or negative moods; greater reactions in OC users vs. NC women, or in caffeine nonusers vs. users A subgroup of 10 NC women will be tested at two points in the menstrual cycle to examine whether responses to PPA are affected by levels of ovarian steroids. Study 2 will investigate responses to 150 mg PPA, 75 mg PPA and 75 mg PPA + 250 mg caffeine in 48 men and 48 women during stress, with half of each group FH+ and half FH- and half caffeine users and half nonusers to determine if reactions to PPA are: potentiated under stress; different for women vs. men, or for caffeine nonusers vs. users; related to changes in plasma catecholamines; greater in individuals at risk for hypertension based on FH.